Mechanoradical-induced degradation in a pharmaceutical blend during high-shear processing.

Abstract:

:Mechanically generated radicals were shown to affect short-term stability of a model pharmaceutical formulation during high-shear processing. A formulation containing an oxidatively sensitive drug, either amorphous or crystalline, and a polymeric excipient was high-shear mixed and the resulting short-term degradation was determined with HPLC. High-shear mixing of the excipients was also carried out before drug addition to isolate effects on excipients versus those directly on the drug. Short-term drug stability was found to be strongly dependent on the amount of shear added to excipients prior to drug addition, regardless of morphology. A mechanism for the observed degradation based on mechanically generated radicals from microcrystalline cellulose is proposed. These results indicate that excipient high-shear exposure needs to be considered in regards to drug stability.

journal_name

Pharm Dev Technol

authors

Polizzi MA,Singhal D,Colvin J

doi

10.1080/10837450802328869

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

457-62

issue

6

eissn

1083-7450

issn

1097-9867

pii

901462168

journal_volume

13

pub_type

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